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• Genomic and Genetic Characterization of Prostate Tumors Treated with Neoadjuvant Intense Androgen Deprivation Therapy

  The purpose of this study was to develop better ways of detecting prostate cancer before and after pre-operative treatment, and to test the feasibility of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of focal prostate cancer both before and after pre-operative treatment with ADT and enzalutamide. In this study, patients with intermediate and high risk prostate cancer received six months of neoadjuvant intense androgen deprivation therapy prior to radical prostatectomy. Biopsies were acquired prior to treatment. Tissue from biopsy and radical prostatectomy were subjected to sequencing and analysis for determination of features associated with response or resistance to treatment.

  Study phs001938

• Cancer Affected Patients - Data Access Committee

  Access to the cancer cohort is made available by completing the data access agreement for review by the data access committee and will be granted to qualified investigators for appropriate use. Individuals requesting access to the data need to comply with the terms of a Data Access Agreement (DAA) and are requested to use the data only in approved and ethical ways.

  Dac EGAC50000000037

• Survival and safety of laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial

  This dataset is the immune profiling of the trial patients. Cryopreserved PBMCs obtained from the patients at different time points were processed to single-cell transcriptomic or TCR libraries using 10x next GEM single Cell 5' v2 kit. We also performed whole exome sequencing (WES) of the tumor to identify the mutation burden. The WES data was generated by sequencing company Novogene. There are total of 69 of single cell libraires, 69 of single cell TCR libraries, and 13 of tumor WES data being generated from 18 trial patients recruited at University of Florida.

  Dataset EGAD50000001639

• PD-1 antibody-bound progenitor-exhausted CD8+ T cells in lymph nodes boost PD-1-blockade anti-tumor immunity in gastrointestinal cancer

  While progenitor-exhausted T cells (Tpex) expressing TCF1 and PD-1 are crucial for the therapeutic effect of immune checkpoint inhibitors (ICIs; therapeutic anti-PD-1 antibodies), the dynamics of ICI-bound Tpex are not fully understood. In this study, we investigated ICI-bound T cells in detail using combined sequencing analysis at the single cell level. By analyzing samples from gastrointestinal cancer patients with or without ICI treatment, we found that Tpex were enriched in proximal lymph nodes (LNs) and proliferated at a high rate after ICI treatment. Importantly, ICI high-bound Tpex in LNs shared T-cell receptor clonotypes with intratumoral exhausted CD8+ T cells (Tex), suggesting their migration to tumor sites after ICI treatment. These findings indicate that ICIs initially target PD-1+CD8+ Tpex in LNs, prompting their proliferation. Subsequently, these cells migrate to tumors and differentiate into Tex, thereby exerting anti-tumor immunity.

  Study JGAS000720

• DNA methylation and transposable element landscapes define human regulatory T cells in tissues and identify their blood recirculating counterpart

  Regulatory T cells (Treg cells) in tissues can perform immunoregulatory and tissue-regenerative functions. Despite these important tasks, human-tissue Treg cells lack understanding, specifically, the epigenetic basis of their differentiation as well as re-circulating tissue-Treg cells are incompletely understood. Here, we performed genome-wide DNA methylation analysis of human Treg cells from skin and blood and embedded this in a multi-omic epigenetic framework including chromatin accessibility and gene-expression. We thereby revealed novel epigenetic programs defining human skin Treg cell differentiation and delineated how these are present on the different epigenetic levels. We discovered that transposable elements are an integral constituent of the demethylation landscape in skin Treg cells. Based on TCR-sequencing and DNA demethylation homologies, our data unveil that blood CCR8+ Treg cells are recirculatory human tissue-Treg cells. Our data provide novel insights in human tissue-Treg biology, required to harness these cells for therapeutic avenues.

  Study EGAS50000000738

• Single-cell RNA sequencing of human skin tumors (BCC, SCC and Melanoma)

  Cancer-associated fibroblasts (CAFs) play a key role in cancer progression and treatment outcome. Here, we elucidate the yet unresolved intra-tumoral CAF variety in three skin cancer types at molecular and spatial single-cell resolution in a large cohort. We show that two out of three CAF subtypes contribute to tumor immune surveillance with distinct mechanisms. Matrix CAFs (mCAFs) ensheath tumor nests and synthesize extracellular-matrix to prevent T cell invasion. Immunomodulatory CAFs (iCAFs), which express proinflammatory and immunomodulatory factors, are only detected in high abundance in aggressive tumors. Strikingly, iCAFs but not tumor cells are (apart from immune cells) the exclusive cell type producing chemokines and, thus, play a key role in immune cell recruitment and activation. Mechanistically, we show that cancer cells transform adjacent healthy fibroblasts into cytokine-expressing iCAFs, which subsequently recruit immune cells and modulate the immune response. In conclusion, targeting CAF variants holds promise for improved efficacy of immunotherapy.

  Study EGAS50000000365

• Whole_Exome_Sequencing_for_Characterization_of_Disease_Causing_Mutations_in_two_Pakistani_Families_Suffering_from_Autosomal_Recessive_Ocular_Disorders_

  We propose to use whole exome Agilent solutionprobes and paired end Illumina sequencing to sequence 4 individualsfrom two families suffering from novel autosomal recessive disease[microphthalmia, MOP (OMIM %251600) and non-syndromic persistenthyperplastic primary vitreous, PHPV (OMIM %611311)]. Selectedcandidate variants will subsequently be genotyped in the remainingfamily members in Pakistan with the aim of identifying the rarehomozygous recessive mutations responsible for the disease phenotype. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001000026

• Genome Sequencing of Hepatocellular Carcinoma at The Human Genome Sequencing Center of Baylor College of Medicine (HGSC-BCM)

  Hepatocellular carcinoma (HCC) accounts for 85-90% of primary liver cancers. We have focused on three major HCC etiologies:hepatitis C virus (HCV), hepatitis B virus (HBV), and nonviral causes. The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. We combined our capability to capture and enrich exome DNA with the next generation sequencing capacity to allow us to detect and characterize the somatic mutation profile of patients with HCC. Patient samples were collected by the Liver Center, Division of Abdominal Transplantation in the Baylor College of Medicine Department of Surgery. Sequencing of HCC is one of the NHGRI Center Initiated Projects in progress in the Human Genome Sequencing Center at Baylor College of Medicine.

  Study phs000509

• Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis

  To identify protein altering variants (PAVs) for glioma we analysed Illumina HumanExome BeadChip exome array data on 1,882 glioma cases and 8,079 controls from three independent European populations. In addition to single variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally tThere was a strong relationship between effect size and SNPs predicted to be damaging (P=2.29x10-49); however, these variants which are most likely to impact on risk, are rare (MAF<5%). While no single variant showed an association which was statistically significant at the genomewide threshold a number of represented promising Notable associations - were seen with the BRCA2:c.9976A>T, p.(Lys3326Ter)BRCA2 p.Lys332X variant, which has been shown documented to influence breast and lung cancer risks (OR=2.3, P=4.00x10-4 for glioblastoma [GBM]) and IDH2:c.782G>A, p.(Arg261His)IDH2 p.Arg261His (OR=3.21, P=7.67x10-3, for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20x10-6). Genome scans of low frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.

  Study EGAS00001001258

• XClone for analyzing somatic copy number alterations

  Somatic copy number alterations (CNAs) are major mutations that contribute to the development and progression of various cancers. Despite a few computational methods proposed to detect CNAs from single-cell transcriptomic data, the technical sparsity of such data makes it challenging to identify allele-specific CNAs, particularly in complex clonal structures. In this study, we present a statistical method, XClone, that strengthens the signals of read depth and allelic imbalance by effective smoothing on cell neighborhood and gene coordinate graphs to detect haplotype-aware CNAs from scRNA-seq data. By applying XClone to multiple datasets with challenging compositions, we demonstrated its ability to robustly detect different types of allele-specific CNAs and potentially indicate whole genome duplication, therefore enabling the discovery of corresponding subclones and the dissection of their phenotypic impacts.

  Study EGAS00001007854

• Selection of somatic escape variants in SERPINA1 in liver tissue of patients with alpha-1 anti-trypsin deficiency - WGS

  Somatic variants accumulate in non-malignant tissues with age. Functional variants leading to clonal advantage of hepatocytes accumulate in the liver from patients with acquired chronic liver disease (CLD). Whether somatic variants are common to CLD from differing aetiologies is unknown. We analysed liver somatic variants in patients with genetic CLD from alpha-1 anti-trypsin (A1AT) deficiency or haemochromatosis. We show that somatic variants in SERPINA1, the gene encoding A1AT, are strongly selected for in A1AT deficiency, with evidence of convergent evolution. Acquired SERPINA1 variants are clustered leading to truncation or coding change at the C-terminus of A1AT. In vitro and in vivo, C-terminal truncation variants reduce disease-associated Z-A1AT polymer accumulation and disruption of the endoplasmic reticulum, supporting the C-terminal domain swap mechanism. Therefore, somatic escape variants from a deleterious germline variant are selected for in A1AT deficiency, suggesting functional somatic variants are disease-specific in CLD and point to disease-associated mechanisms.

  Dataset EGAD00001015430

• Comprehensive genetic analysis of uveal melanoma heterogeneity during metastatic progression

  Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance. Thus whole exome sequencing and transcriptomics have been performed on constitutional, primary tumor and metastatic samples from 28 UM patients.

  Study EGAS00001002761

• Data Access Committee for Translational analyses from a phase II study of pembrolizumab and epigenetic modification with azacitidine in platinum-resistant epithelial ovarian cancer

  This DAC is responsible for request review and handling related to the study above.

  Dac EGAC50000000697

• SPECTA: NGS Screening Program for Efficient Clinical Trial Access

  SPECTA comprises a network of participating European clinical sites and NGS screening platforms that can screen individual patients for multiple molecular targets and potentially allow the design of trials that will match the specific biology of the diseases affecting specific patients with cancer.

  Dataset EGAD00001000894

• Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Severe Asthma Research Program (SARP)

  Cohort Description The Severe Asthma Research Program (SARP) has been investigating the clinical, physiologic and molecular phenotypes of asthma since 2000. It is currently following ~400 deeply phenotyped asthma patients. Data Being Submitted Wave 1 questionnaire data includes 397 variables for up to 375 SARP participants in C4R.Wave 2 questionnaire data includes 448 variables for up to 289 SARP participants in C4R.Dried Blood Spot/Serosurvey data includes 7 variables for up to 290 SARP participants in C4R.Derived data includes 43 variables for up to 463 SARP participants in C4R.Phenotype data includes 113 variables for up to 463 SARP participants in C4R.

  Study phs002913

• Sequencing data of the ampulla and fimbriae of the fallopian tube in pre-menopausal women

  A total of 10 pre-menopausal patients were recruited for this study. Sequencing of both the fimbriae and ampullary region of the fallopian tubes was performed using 10x Genomics single-cell RNA-seq and ATAC-seq. For one patient, data were sequenced across 4 lanes, while the remaining patients' data were sequenced in 2 lanes each, resulting in a total of 44 sequencing datasets for each platform.

  Dataset EGAD50000000889

• Dac for "Development of a fully human glioblastoma-in-brain-spheroid model for accelerated translational research"

  This is the DAC for "Development of a fully human glioblastoma-in-brain-spheroid model for accelerated translational research" of Philipp Koch (philipp.koch@zi-mannheim.de), Frank Winkler (Frank.Winkler@med.uni-heidelberg.de), Moritz Mall( m.mall@dkfz-heidelberg.de)

  Dac EGAC50000000480

• Mayo Clinic and Illumina Collaborative Early Stage Ovarian Cancer (ESOC) Study

  Twenty five patients with early stage carcinoma (Stage I and II) of the ovary were consented for this study. As part of a collaborative agreement with Illumina Inc, Tumor-DNA and patient matched normal DNA from blood underwent whole genome sequencing and microarray genotyping and RNA underwent RNASeq. Tissue also underwent IHC staining for TP53 mutations. The aim of the study was to profile the genomic landscape of these early tumors to discover biomarkers for early detection or subgrouping into different genomic or outcome subgroups. Analyses performed include somatic mutation analysis, RNASeq mutation analysis, LOH analysis, structural variant detection. The current release of this study focusses on 17 patients with serous carcinoma and stage 1 or 2 and with high grade (3 or 4).

  Study phs000897

• The EGA joins EUCAIM, the European project powering AI and imaging in cancer research

  EUCAIM (EUropean Federation for CAncer IMages) is the cornerstone of the European Cancer Imaging Initiative, one of the flagships of the Europe’s Beating Cancer Plan (EBCP). The European Genome-Phenome Archive (EGA), as member of the EUCAIM consortium, attended the kick-off meeting organized this week in Brussels for the launch of the Initiative. The EGA will contribute to the project with the experience gained in the deployment of our federated network, the Federated EGA (FEGA), and the experience gained as partners of EuCanImage (AI4HI initiative) contributing to the definition of common data models, ontologies and data standards. The ultimate goal of the project is to unlock the power of imaging and Artificial Intelligence for the benefit of cancer patients, clinicians and researchers. The consortium will deploy a pan-European digital federated infrastructure hosting cancer-related images, and associated pathology, molecular and laboratory data from Real-World. This endeavour will provide a comprehensive dashboard for imaging data discovery, federated search, metadata harvesting, annotation and distributed data processing. EUCAIM joins 76 partners, gathering the experience and previous effort made by the different repositories of the AI4HI initiative, European Research Infrastructures and national/regional repositories. Find out more information about the EUCAIM launch here

  Blog the-ega-joins-eucaim

• sWGS for 92 samples of mCRC

  Shallow Whole Genome Sequencing of 92 mCRC samples. Chromosomal copy number alterations analysis was performed with the samples to predict response to bevacizumab.

  Dataset EGAD50000000992

• Oxford Nanopore long-read sequencing data of high-grade serous ovarian cancer

  This dataset comprises whole-genome Oxford Nanopore long-read sequencing data from six high-grade serous ovarian cancer (HGSOC) patients, including cryopreserved, pre-treatment tumor tissues and matched peripheral blood samples (12 samples in total). High-molecular-weight DNA was prepared using the SQK-LSK114 Ligation Sequencing Kit and sequenced on FLO-PRO114M flow cells (R10.4.1). Basecalling was conducted using the super-accurate (SUP) model, enabling simultaneous detection of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The dataset includes BAM files containing base modification information for downstream genomic and epigenomic analyses.

  Dataset EGAD50000001509

• Visium CytAssist Spatial Gene Expression analysis for glioblastoma

  The glioblastoma spatial transcriptomics dataset was generated from 4 FFPE fixed adult glioblastoma samples, using the 10x Genomics Visium platform, producing raw FASTQ files, spatial feature matrices (.h5, .mtx, .tsv), and paired histology images (.tif). Spot-level transcript counts were aligned to tissue architecture and processed in Seurat, with results stored as .rds objects. Data visualization was performed using SpatialFeaturePlot, and quantitative analyses were supported by custom Matlab scripts. The dataset provides both raw and processed files, offering reproducible spatially resolved transcriptomic profiles of glioblastoma tissue sections

  Dataset EGAD50000001767

• Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis

  This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.

  Study EGAS00001000515

• Use_of_Deep_Sequencing_to_Dectect_Clonal_Mutations_In_Sun_Exposed_Skin_Epidermis_PART2

  This study aims to define the landscape of somatic mutations in sun exposed human skin by deep sequencing, analyse their frequency and use the data to infer the effect of mutations on proliferating cell behaviour. The frequency of each mutation will reflect the size of the clone of cells in the tissue sample. By analyzing small samples, clones with as few as 100 cells will be detectable. Allele frequency distributions for each mutation will be used to infer cell fate using published methods (Klein et al. 2010). This study will shed unprecedented light on the early clonal events that lead to the emergence of cancer.

  Study EGAS00001000603

• Identification of genes involved in congenital disorders of glycosylation and 3-methylglutaconic aciduria (2018-03-14)

  Identification of genes involved in congenital disorders of glycosylation and 3-methylglutaconic aciduria. There are more than 100 genes known for congenital disorders of glycosylation and new disorders are discovered each year. WE included patients with a so far unsolved glycosylation disease. The diagnostic group 3-methyglutaconic aciduria is a heterogenous group of disorders mostly caused by abnormal phospholipid synthesis or in association with mitochondrial dysfunction. We included patients with a so far unsolved disease and 3-methylglutaconic aciduria. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ . This dataset contains all the data available for this study on 2018-03-14.

  Dataset EGAD00001004038